SZKOLENIE PODYPLOMOWE/POSTGRADUATE EDUCATION Endokrynologia Polska/Polish Journal of Endocrinology Tom/Volume 62; Numer/Number 2/2011 ISSN 0423–104X Gynecomastia — a difficult diagnostic problem Ginekomastia — trudny problem diagnostyczny Marek Derkacz1, Iwona Chmiel-Perzyńska2, Andrzej Nowakowski1 1Department of Endocrinology, Medical University, Lublin, Poland 2Department of Family Medicine, Medical University, Lublin, Poland Abstract Gynecomastia is a benign, abnormal, growth of the male breast gland which can occur unilaterally or bilaterally, resulting from a prolife- ration of glandular, fibrous and adipose tissue. Gynecomastia is characterised by the presence of soft, 2–4 cm in diameter, usually discus- shaped enlargement of tissues under the nipple. It is estimated that this pathology occurs in 32–65% of men over the age of 17. Gynecoma- stia is a psychosocial problem and may lead to a perceived lowering of quality of life. The main cause of gynecomastia is a loss of equilibrium between oestrogens and androgens. Increased sensitivity for oestrogens of the breast gland, or local factors (e.g. an excessive synthesis of oestrogens in breast tissues or changes in oestrogen and androgen receptors) may cause gynecomastia. Also, prolactin, thyroxine, cortisol, human chorionic gonadotropin, leptin and receptors for human chorionic gonadotropin, prolactin and luteinizing hormone localised in tissues of the male breast may participate in the etiopathogenesis of gyneco- mastia. Usually three types of gynecomastia are distinguished: physiological, idiopathic and pathological gynecomastia. The latter is the consequ- ence of relative or absolute excess of oestrogens. In this paper, frequent as well as casuistic causes of gynecomastia will be described. A diagnosis of gynecomastia is usually possible after a palpation examination. Ultrasonographic, mammographic or histopathological examinations are useful in aiding diagnosis. The five degree scale devised by Tanner and Marshall is useful in estimating disease progres- sion. (Pol J Endocrinol 2011; 62 (2): 190–201) Key words: gynecomastia, etiopathogenesis, diagnosis, psychosocial problem Streszczenie Ginekomastia jest łagodnym, nieprawidłowym, występującym jedno lub obustronnie wzrostem objętości gruczołów piersiowych u męż- czyzn, wynikającym z rozrostu tkanki gruczołowej, włóknistej i tłuszczowej. Zmiany charakteryzują się obecnością miękkiego, zwykle dyskoidalnego powiększenia tkanek o średnicy 2–4 cm, zlokalizowanego pod brodawką sutkową. Szacuje się, że występuje u 32–65% mężczyzn powyżej 17. roku życia. Ginekomastia stanowi problem psychospołeczny i prowadzi do pogorszenia jakości życia mężczyzn. Główną przyczyną ginekomastii są zaburzenia równowagi pomiędzy estrogenami a androgenami. Do jej rozwoju może prowadzić rów- nież zwiększona wrażliwość tkanki gruczołu piersiowego na estrogeny i/lub czynniki miejscowe (takie jak np. nadmierna produkcja estrogenów w tkankach gruczołu piersiowego, a także zmiany dotyczące receptorów dla estrogenów i androgenów). Również prolakty- na, tyroksyna, kortyzol, ludzka gonadotropina kosmówkowa, leptyna oraz receptory dla b-hCG, prolaktyny i luteotropiny zlokalizowane w tkance męskich gruczołów sutkowych mogą brać udział w rozwoju ginekomastii. Wyróżnia się ginekomastię fizjologiczną, idiopatyczną i patologiczną, będącą wynikiem bezwzględnego lub względnego nadmiaru estro- genów. W pracy opisano zarówno częste, jak i kazuistyczne przyczyny ginekomastii. Rozpoznanie stawiane jest zwykle na podstawie badania palpacyjnego. W diagnostyce wykorzystywane są techniki obrazowe, takie jak ultrasonografia czy mammografia lub badanie histopatologiczne. W ocenie zaawansowania ginekomastii przydatna jest 5-stopniowa skala Tannera i Marshalla. (Endokrynol Pol 2011; 62 (2): 190–201) Słowa kluczowe: ginekomastia, przyczyny, diagnostyka, aspekty psychospołeczne Introduction to four centimetres in diameter, located below the nip- ple. The enlargement of the glands is usually bilateral The term gynecomastia (Greek: gyne = woman, ma- and symmetrical; however, gynecomastia may also oc- stos = breast) was introduced in the first century A.D. cur unilaterally, usually on the left side [1]. The enlar- by Galen. Gynecomastia is marked by a benign, abnor- ged volume of the breast glands in some cases may be mal, unilateral or bilateral volumetric increase in men’s accompanied by tenderness and pain, the cause of breast glands as a result of the proliferation of glandu- which is usually the rapid growth of glandular tissue. lar, fibrous, and adipose tissue. Changes are characteri- Its occurrence among men over the age of 17 is estima- sed by a soft, usually discoidal tissue enlargement two ted at 32–65%. In some age groups, such changes may Marek Derkacz MD, Department of Endocrinology, Jaczewskiego 8, 20–954 Lublin, Poland, tel./fax: +48 81 724 46 68, e-mail: [email protected] 190 Endokrynologia Polska/Polish Journal of Endocrinology 2011; 62 (2) occur in up to 72% of men [2–4]. Diagnoses are often Table I. Gynecomastia — causes and frequency of their made on the basis of palpation exams: the diameter of occurrence [2] the palpable lesion should then exceed 2 cm. In dia- Tabela I. Ginekomastia — przyczyny i częstość ich wystę- gnosing gynecomastia, visual techniques such as ultra- powania [2] sonography or mammography may prove useful. It may Cause Frequency also be diagnosed on the basis of a histopathology exam, of occurrence which necessitates invasive diagnostic methods [2]. In the assessment of gynecomastia, Tanner and Marshall’s Idiopathic 25% five-stage scale evaluating the proper development of Sexual maturity 25% the breast glands is useful [5]. Medications 10–20% Hepatic cirrhosis or poor nourishment 8% The causes of gynecomastia Primary hypogonadism 8% Orchidoncus 3% The commonest cause of gynecomastia is disturbance Secondary hypogonadism 2% of the balance between oestrogens (exhibiting a stimu- Hyperthyreosis 2% latory action on the breast gland) and androgens (which Kidney diseases 1% have an inhibitory function) [6–8]. The changes frequ- Others 6% ently occur in response to an increased production and/ /or activity of oestrogens and a decreased production and/or activity of testosterone. Increased sensitivity of Infancy the breast tissue to oestrogen may also lead to the de- Transient gynecomastia is observed in 60–90% of in- velopment of gynecomastia, at which time the deve- fants, being a result of the activity of maternal oestro- lopment of changes occurs despite the proper concen- gen found in the child’s organism. Changes usually give tration of these hormones in the blood. A major role in way to idiopathic regression within a few months. the pathogenesis of changes seems to be played by lo- cal factors, such as excessive production of oestrogens Adolescence in the breast tissues, being a result of increased activity Gynecomastia as a result of excessive production of of aromatase, their decreased degradation, and also oestrogen and its precursors in relation to testosterone changes concerning oestrogen and androgen receptors is found in 20–70% of pubertal boys. The peak of symp- [9]. Likewise, prolactin (PRL), thyroxin, cortisol, human tom occurrence is experienced at 13–14 years of age. chorionic gonadotrophin (b-hCG), leptin, and receptors Changes usually give way to spontaneous regression for b-hCG, prolactin, and luteotropin localised in the in six months to three years. It seems that in the patho- tissue of men’s mammary glands may play a part in the genesis of gynecomastia, besides the upsetting of the development of gynecomastia [10–12]. hormonal balance, a major role may be played by an Hyperprolactinaemia, once considered to be the elevated level of leptin, which has been observed in boys primary cause of gynecomastia, in fact plays a less si- with pubescent gynecomastia. This compound incre- gnificant role in its origination. In most patients with ases the activity of aromatase in the fatty tissue as well gynecomastia, the level of PRL in the blood is within as other tissues of the breast gland. This leads to a rise the normative range [12]. An elevated level of PRL may in the concentration of oestrogens and/or the oestrogen/ however inhibit the secretion of gonadotropins, evo- /androgen relation. The impact of leptin on the develop- king secondary hypogonadism, although gynecomastia ment of gynecomastia is also probably connected to its does not occur in all patients with hyperprolactinaemia. direct functional stimulation of the growth of mammary Enlargement of the breast glands is also affected by an gland cells or the increase of sensitivity of these cells to excess of growth hormone (GH) and insulin-like growth oestrogen with concurrent functional activation of oestro- SZKOLENIE factor (IGF). The major impact of these substances on gen receptors in the breast gland tissue [14]. A signifi- PODYPLOMOWE the growth of breast gland size, and the increase of the cant overgrowth of glandular tissue persisting beyond proliferation index of the epithelium, have been demon- 17 years of age usually requires the application of the strated in experimental studies [13] (Table I). appropriate treatment. Cases of gynecomastia (often oc- curring unilaterally) are observed among adolescent boys Types of gynecomastia in the course of neurofibromatosis [15]. Physiological gynecomastia Physiological gynecomastia is most often defined as Senescence symptomless gynecomastia occurring in three periods About 30–85% of cases of physiological gynecomastia